1. Field of the Invention
The present invention generally relates to recombinant human progenitor cells, and engineered functional effector cells including engineered human thymocytes, and engineered human T cells, and methods of treating subjects therewith.
2. Description of the Related Art
CD8+ cytotoxic T-lymphocytes (CTLs) partially control human immunodeficiency virus (HIV) in almost all infected persons, but eventually fail due to viral mutation, downregulation of Human Leukocyte Antigen (HLA), lack of CD4+ T-cell help, and CTL clonal exhaustion. While HIV infections can be controlled in many individuals with antiretroviral drugs, these are expensive and associated with significant toxicities. Due to viral reservoirs, if therapy is terminated, virus replication and disease progression resume, requiring patients to remain on these medications permanently. To date there has only been a single reported case of cured chronic HIV infection in an adult, via bone marrow transplant from a donor lacking the normal gene for C-C chemokine receptor type 5 (CCR5), which is a cell receptor required for most strains of HIV to infect cells. However, the mortality rate of this procedure is about 40%, and matched bone marrow with this genetic profile is almost nonexistent for most ethnic groups, rendering this approach impractical for broader clinical applicability. Several recent studies have attempted to remove CCR5 from hematopoietic stem cells and/or deliver anti-HIV genes to protect cells from HIV infection in humans, but these studies face limitations due to unknowns regarding levels of transduced cell engraftment required to generate an HIV-resistant immune system.